A dose-finding investigation was conducted with mitoxantrone administered as 14-day continuous infusions to patients with hormone-refractory metastatic adenocarcinoma of the prostate. Fifteen men participated in four dosage groups: mitoxantrone 1.0, 1.25, 1.4, and 1.5 mg/m2/day; a treatment cycle was defined as a dose of mitoxantrone given over 2 weeks, followed by 2 weeks of monitoring prior to the next course. The patients received 1 to 10 courses, with the majority receiving 1 to 3. The maximum tolerated dose was 1.25 mg/m2/day for 14 days of continuous infusion. Two patients discontinued treatment because of gastrointestinal effects. Most adverse clinical experiences were mild or moderate in intensity. A decrease in prostate-specific antigen (PSA) response was seen after one course in 6 of 14 patients who had PSA measurements. Stable disease was achieved in 40% of the evaluable patients, and some quality of life parameters improved. Further clinical trials with mitoxantrone are indicated in patients with prostatic cancer, especially in those who have had less previous treatment.